Recent studies with tiling arrays have revealed more genomic transcription than previously anticipated. Whole new groups of non-coding transcripts (NCTs) have been detected. Some of these NCTs, including miRNAs, can regulate gene expression. To date, most known NCTs studied have been relatively short, but several important regulatory NCTs, including XIST, MALAT-1, BC1 and BC200, are considerably larger in length and represent a novel class of long, non-coding RNA species. Whole-genome tiling arrays were utilized to identify novel long NCTs across the entire human genome. Our results have identified a new group of long (>400 nt), abundantly expressed NCTs and have found that a subset of these are also highly evolutionarily conserved. In this report, we have begun to characterize 15 long, conserved NCTs. Quantitative real-time RT-PCR was used to analyze their expression in different normal human tissue and also in breast and ovarian cancers. We found altered expression of many of these NCTs in both cancer types. In addition, several of these NCTs have consistent mutations when sequences of normal samples were compared with a panel of cancer-derived cell lines. One NCT was found to be consistently mutated in a panel of endometrial cancers compared with matched normal blood. These NCTs were among the most abundantly expressed transcripts detected. There are probably many long, conserved NCTs, albeit with lower levels of expression. Although the function of these NCTs is currently unknown, our study indicates that they may play an important function in both normal cells and in cancer development.